Platelets and Intravascular Immunity: Guardians of the Vascular Space During Bloodstream Infections and Sepsis

Despite their humble origins as anuclear fragments of megakaryocytes, platelets have emerged as versatile mediators of thrombosis and immunity. The diverse spectrum of platelet functions are on full display during the host response to severe infection and sepsis, with platelets taking center-stage in the intravascular immune response to blood-borne pathogens. Platelets are endowed with a comprehensive armamentarium of pathogen detection systems that enable them to function as sentinels in the bloodstream for rapid identification of microbial invasion. Through both autonomous anti-microbial effector functions and collaborations with other innate immune cells, platelets orchestrate a complex intravascular immune defense system that protects against bacterial dissemination. As with any powerful immune defense system, dysregulation of platelet-mediated intravascular immunity can lead to profound collateral damage to host cells and tissues, resulting in sepsis-associated organ dysfunction. In this article, the cellular and molecular contributions of platelets to intravascular immune defenses in sepsis will be reviewed, including the roles of platelets in surveillance of the microcirculation and elicitation of protective anti-bacterial responses. Mechanisms of platelet-mediated thromboinflammatory organ dysfunction will be explored, with linkages to clinical biomarkers of platelet homeostasis that aid in the diagnosis and prognostication of human sepsis. Lastly, we discuss novel therapeutic opportunities that take advantage of our evolving understanding of platelets and intravascular immunity in severe infection.